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Cardiovascular Effects of β-Agonists in Patients With Asthma and COPD*: A Meta-Analysis

Shelley R. Salpeter, MD; Thomas M. Ormiston, MD; Edwin E. Salpeter, PhD
Author and Funding Information

*From Santa Clara Valley Medical Center (Drs. S.R. Salpeter and Ormiston), San Jose, CA; and Cornell University (Dr. E.E. Salpeter), Ithaca, NY.

Correspondence to: Shelley R. Salpeter, MD, 751 S Bascom Ave, San Jose, CA 95128; e-mail: salpeter@stanford.edu



Chest. 2004;125(6):2309-2321. doi:10.1378/chest.125.6.2309
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Background: β-Adrenergic agonists exert physiologic effects that are the opposite of those of β-blockers. β-Blockers are known to reduce morbidity and mortality in patients with cardiac disease. β2-Agonist use in patients with obstructive airway disease has been associated with an increased risk for myocardial infarction, congestive heart failure, cardiac arrest, and acute cardiac death.

Objectives: To assess the cardiovascular safety of β2-agonist use in patients with obstructive airway disease, defined as asthma or COPD.

Methods: A meta-analysis of randomized placebo-controlled trials of β2-agonist treatment in patients with obstructive airway disease was performed, to evaluate the short-term effect on heart rate and potassium concentrations, and the long-term effect on adverse cardiovascular events. Longer duration trials were included in the analysis if they reported at least one adverse event. Adverse events included sinus and ventricular tachycardia, syncope, atrial fibrillation, congestive heart failure, myocardial infarction, cardiac arrest, or sudden death.

Results: Thirteen single-dose trials and 20 longer duration trials were included in the study. A single dose of β2-agonist increased the heart rate by 9.12 beats/min (95% confidence interval [CI], 5.32 to 12.92) and reduced the potassium concentration by 0.36 mmol/L (95% CI, 0.18 to 0.54), compared to placebo. For trials lasting from 3 days to 1 year, β2-agonist treatment significantly increased the risk for a cardiovascular event (relative risk [RR], 2.54; 95% CI, 1.59 to 4.05) compared to placebo. The RR for sinus tachycardia alone was 3.06 (95% CI, 1.70 to 5.50), and for all other events it was 1.66 (95% CI, 0.76 to 3.6).

Conclusion: β2-Agonist use in patients with obstructive airway disease increases the risk for adverse cardiovascular events. The initiation of treatment increases heart rate and reduces potassium concentrations compared to placebo. It could be through these mechanisms, and other effects of β-adrenergic stimulation, that β2-agonists may precipitate ischemia, congestive heart failure, arrhythmias, and sudden death.

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